Positive topline results from Phase III studies of AvyCaz (ceftazidime-avibactam) in urinary tract infections- Allergan

Allergan announced positive topline results from RECAPTURE 1 and 2, the pivotal Phase III studies evaluating the antibiotic AvyCaz (ceftazidime-avibactam) as a treatment for adult hospitalized patients with complicated urinary tract infections (cUTI), including pyelonephritis. The global RECAPTURE 1 and 2 Phase III studies evaluated the safety and efficacy of AvyCaz administered intravenously as a two-hour infusion (2000/500mg every 8 hours), compared to doripenem, administered intravenously as a 30-minute infusion (500mg every 8 hours), in hospitalized adult patients with cUTI, including pyelonephritis. Allergan plans to submit this data as a supplemental New Drug Application to the FDA by the end of 2015.

Data from the studies were analysed as a single-pooled dataset with the agreement of the US FDA and the EMA. In the RECAPTURE 1 and RECAPTURE 2 Phase III studies, AvyCaz met the objective of statistical non-inferiority compared to doripenem for both the EMA primary and FDA co-primary endpoints. AvyCaz was also effective in treating cUTI patients infected with ceftazidime-resistant bacteria. The most commonly reported adverse events were headache, nausea, constipation and diarrhea. No new safety concerns were identified upon review of the most frequent events up to the late follow-up visit (45�52 calendar days after randomization).

Comment: Ceftazidime-avibactam was approved by the FDA as AvyCaz in February 2015 for the treatment of cUTI including pyelonephritis and complicated intra-abdominal infections (cIAI), in combination with metronidazole, caused by designated susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa for patients 18 years of age and older. AvyCaz received a priority review based on Phase II data from the company's clinical development program and supporting in vitro data, and as such should be reserved for use in patients who have limited or no alternative treatment options. In the EU, the regulatory submission seeking approval for a range of indications, was accepted and validated by the European Medicines Agency in May 2015 and is currently under review.